{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360004234671834752.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1093/nar/gkx1190"}},{"identifier":{"@type":"URI","@value":"http://academic.oup.com/nar/article-pdf/46/3/1180/23941388/gkx1190.pdf"}},{"identifier":{"@type":"PMID","@value":"29186616"}},{"identifier":{"@type":"HANDLE","@value":"1887/75818"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"JUNB governs a feed-forward network of TGFβ signaling that aggravates breast cancer invasion"}],"description":[{"notation":[{"@value":"It is well established that transforming growth factor-β (TGFβ) switches its function from being a tumor suppressor to a tumor promoter during the course of tumorigenesis, which involves both cell-intrinsic and environment-mediated mechanisms. We are interested in breast cancer cells, in which SMAD mutations are rare and interactions between SMAD and other transcription factors define pro-oncogenic events. Here, we have performed chromatin immunoprecipitation (ChIP)-sequencing analyses which indicate that the genome-wide landscape of SMAD2/3 binding is altered after prolonged TGFβ stimulation. De novo motif analyses of the SMAD2/3 binding regions predict enrichment of binding motifs for activator protein (AP)1 in addition to SMAD motifs. TGFβ-induced expression of the AP1 component JUNB was required for expression of many late invasion-mediating genes, creating a feed-forward regulatory network. Moreover, we found that several components in the WNT pathway were enriched among the late TGFβ-target genes, including the invasion-inducing WNT7 proteins. Consistently, overexpression of WNT7A or WNT7B enhanced and potentiated TGFβ-induced breast cancer cell invasion, while inhibition of the WNT pathway reduced this process. Our study thereby helps to explain how accumulation of pro-oncogenic stimuli switches and stabilizes TGFβ-induced cellular phenotypes of epithelial cells."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380004234671835399","@type":"Researcher","foaf:name":[{"@value":"Anders Sundqvist"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004234671834763","@type":"Researcher","foaf:name":[{"@value":"Masato Morikawa"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004234671835136","@type":"Researcher","foaf:name":[{"@value":"Jiang Ren"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004234671835403","@type":"Researcher","foaf:name":[{"@value":"Eleftheria Vasilaki"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004234671834756","@type":"Researcher","foaf:name":[{"@value":"Natsumi Kawasaki"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004234671835274","@type":"Researcher","foaf:name":[{"@value":"Mai Kobayashi"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004234671835269","@type":"Researcher","foaf:name":[{"@value":"Daizo Koinuma"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004234671835018","@type":"Researcher","foaf:name":[{"@value":"Hiroyuki Aburatani"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004234671835141","@type":"Researcher","foaf:name":[{"@value":"Kohei Miyazono"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004234671835271","@type":"Researcher","foaf:name":[{"@value":"Carl-Henrik Heldin"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004234671835017","@type":"Researcher","foaf:name":[{"@value":"Hans van Dam"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004234671835137","@type":"Researcher","foaf:name":[{"@value":"Peter ten Dijke"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"03051048"},{"@type":"EISSN","@value":"13624962"}],"prism:publicationName":[{"@value":"Nucleic Acids Research"}],"dc:publisher":[{"@value":"Oxford University Press (OUP)"}],"prism:publicationDate":"2017-11-23","prism:volume":"46","prism:number":"3","prism:startingPage":"1180","prism:endingPage":"1195"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","dc:rights":["http://creativecommons.org/licenses/by-nc/4.0/"],"url":[{"@id":"http://academic.oup.com/nar/article-pdf/46/3/1180/23941388/gkx1190.pdf"}],"createdAt":"2017-11-19","modifiedAt":"2022-08-07","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Embryo,%20Nonmammalian","dc:title":"Embryo, Nonmammalian"},{"@id":"https://cir.nii.ac.jp/all?q=Breast%20Neoplasms","dc:title":"Breast Neoplasms"},{"@id":"https://cir.nii.ac.jp/all?q=Smad2%20Protein","dc:title":"Smad2 Protein"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Line","dc:title":"Cell Line"},{"@id":"https://cir.nii.ac.jp/all?q=Transforming%20Growth%20Factor%20beta1","dc:title":"Transforming Growth Factor beta1"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Line,%20Tumor","dc:title":"Cell Line, Tumor"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Gene%20Regulatory%20Networks","dc:title":"Gene Regulatory Networks"},{"@id":"https://cir.nii.ac.jp/all?q=Neoplasm%20Invasiveness","dc:title":"Neoplasm Invasiveness"},{"@id":"https://cir.nii.ac.jp/all?q=Smad3%20Protein","dc:title":"Smad3 Protein"},{"@id":"https://cir.nii.ac.jp/all?q=Wnt%20Signaling%20Pathway","dc:title":"Wnt Signaling Pathway"},{"@id":"https://cir.nii.ac.jp/all?q=Zebrafish","dc:title":"Zebrafish"},{"@id":"https://cir.nii.ac.jp/all?q=Feedback,%20Physiological","dc:title":"Feedback, Physiological"},{"@id":"https://cir.nii.ac.jp/all?q=Cancer%20och%20onkologi","dc:title":"Cancer och onkologi"},{"@id":"https://cir.nii.ac.jp/all?q=Binding%20Sites","dc:title":"Binding Sites"},{"@id":"https://cir.nii.ac.jp/all?q=Base%20Sequence","dc:title":"Base Sequence"},{"@id":"https://cir.nii.ac.jp/all?q=Gene%20Expression%20Profiling","dc:title":"Gene Expression Profiling"},{"@id":"https://cir.nii.ac.jp/all?q=Gene%20regulation,%20Chromatin%20and%20Epigenetics","dc:title":"Gene regulation, Chromatin and Epigenetics"},{"@id":"https://cir.nii.ac.jp/all?q=High-Throughput%20Nucleotide%20Sequencing","dc:title":"High-Throughput Nucleotide Sequencing"},{"@id":"https://cir.nii.ac.jp/all?q=Epithelial%20Cells","dc:title":"Epithelial Cells"},{"@id":"https://cir.nii.ac.jp/all?q=Gene%20Expression%20Regulation,%20Neoplastic","dc:title":"Gene Expression Regulation, Neoplastic"},{"@id":"https://cir.nii.ac.jp/all?q=Wnt%20Proteins","dc:title":"Wnt Proteins"},{"@id":"https://cir.nii.ac.jp/all?q=Cancer%20and%20Oncology","dc:title":"Cancer and Oncology"},{"@id":"https://cir.nii.ac.jp/all?q=Female","dc:title":"Female"},{"@id":"https://cir.nii.ac.jp/all?q=Protein%20Binding","dc:title":"Protein Binding"},{"@id":"https://cir.nii.ac.jp/all?q=Transcription%20Factors","dc:title":"Transcription Factors"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000782482910080","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"15H05774"},{"@type":"JGN","@value":"JP15H05774"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15H05774/"}],"notation":[{"@language":"ja","@value":"ＴＧＦーβシグナルによる転写調節とがん悪性化機構"},{"@language":"en","@value":"Transcriptional regulation by TGF-beta signaling and its relation to progression of cancer"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050001202940769280","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Phenotypic complementation establishes requirements for specific POU domain and generic transactivation function of Oct-3/4 in embryonic stem 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